Posterior mean rates of evolution of H3N2 <i>vs.</i> H1N1 viruses.

<p>Results are shown on a - scale (in substitutions/site/year). The gray line represents the first bisector (line of equation ), while the red line represents the linear fit to the data. Bars: limits of the 95% Highest Posterior Densities.</p

Phylodynamics of the Emergence of Influenza Viruses after Cross-Species Transmission

<div><p>Human populations are constantly exposed to emerging pathogens such as influenza A viruses that result from cross-species transmissions. Generally these sporadic events are evolutionary dead-ends, but occasionally, viruses establish themselves in a new host that offers a novel genomic context to which the virus must adjust to avoid attenuation. However, the dynamics of this process are unknown. Here we present a novel method to characterize the time it takes to G+C composition at third codon positions (GC3 content) of influenza viruses to adjust to that of a new host. We compare the inferred dynamics in two subtypes, H1N1 and H3N2, based on complete genomes of viruses circulating in humans, swine and birds between 1900–2009. Our results suggest that both subtypes have the same fast-adjusting genes, which are not necessarily those with the highest absolute rates of evolution, but those with the most relaxed selective pressures. Our analyses reveal that NA and NS2 genes adjust the fastest to a new host and that selective pressures of H3N2 viruses are relaxed faster than for H1N1. The asymmetric nature of these processes suggests that viruses with the greatest adjustment potential to humans are coming from both birds and swine for H3N2, but only from birds for H1N1.</p></div

Estimation of adjustment times.

<p>Schematic representation of the method developed to estimate adjustment times. A host-switch event occurred along the red branch, and a GC3 cluster change occurred along the blue branch. Time flows from the past to the present (bottom axis), and divergence times are estimated for nodes (see vertical broken lines). The two durations of interest are and . See text for details.</p

Factor effects in the linear model (ANOVA) that was fitted to adjustment times (in years).

<p>The directions of host change are avian-to-human (A-H), avian-to-swine (A-S), human-to-avian (H-A), human-to-swine (H-S), swine-to-avian (S-A) and swine-to-human (S-H). Adjustment times are in years. See text for details.</p

GC3 adjustment times of H3N2 <i>vs.</i> H1N1 viruses.

<p>Results are shown on a - scale (in years). The gray line represents the first bisector (line of equation ), while the red line represents the linear fit to the data. Bars: SEMs (95% Highest Posterior Densities, not shown, tend to be larger – see Fig. S27 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082486#pone.0082486.s001" target="_blank">File S1</a>). : the HA value for H3N2 was tentatively derived using branches around the root node.</p